Gamma probe and ultrasound guided fine needle aspiration cytology of the sentinel node (GULF) trial - overview of the literature, pilot and study protocol

Abstract

BackgroundSentinel node (SN) biopsy (SNB) detects clinically occult metastases of breast cancer and melanoma in 20–30%. Wound infections, seroma and lymph edema occur in up to 10%. Targeted ultrasound (US) of the SN, (with fine needle aspiration cytology (FNAC) if appropriate) has been investigated as a minimally invasive alternative, but reported sensitivity rates are too low to replace SNB. Our hypothesis is that the use of a handheld gamma probe concomitant with US may improve sensitivity.Our aim is to provide an overview of the current literature on preoperative nodal staging of clinical N0 melanoma patients, report on a pilot, and present a study protocol for a minimally invasive alternative to the SNB: Gamma probe and Ultrasound guided Fine needle aspiration cytology of the sentinel node (GULF trial).MethodsThe GULF trial is a multicenter open single arm observational trial. Newly diagnosed cT1b-4N0M0 cutaneous melanoma or cT1-3N0M0 breast cancer patients, aged >18 years, presenting for SNB are eligible. 120 patients will be included for preoperative targeted gamma probe guided US and FNAC of the SN. Afterwards all patients proceed to surgical SNB. Primary endpoint is the sensitivity of FNAC. Secondary endpoints include SN identification rate and the histopathological compatibility of Core Needle Biopsy and FNAC vs. SNB. Secondary endpoints were investigated in a pilot with 10 FNACs and marker placements, and 10 FNACs combined with Core Needle Biopsy.ResultsA pilot in 20 patients showed that SN identification rate was 90%, supporting the feasibility of this technique.DiscussionThere is broad experience with US (in combination with FNAC) prior to SNB, but sensitivity and specificity are too low to completely abandon SNB. Promising alternative techniques potentially will replace SNB in the future but more evidence is needed in the form of prospective studies. Accurate identification of the SN for US-FNAC has been proven feasible in our pilot. When adequate sensitivity can be reached, US-FNAC provides a minimally invasive alternative for the surgical SNB procedure.Trial registrationThe GULF trial is registered in the Netherlands Trial Registry (NTR), ID: NRT5193. May 1st 2015.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-017-3236-2) contains supplementary material, which is available to authorized users.

Gamma probe and ultrasound-guided fine needle aspiration cytology of the sentinel node (GULF) trial

“…The Mini 900 scintillation monitor with a sodium iodide crystal was used on 44 samples, and showed a signal more than twice the background signal in 75% of the samples. This supports the high accuracy of SN identification using FNAC with gamma probe and US guidance, as was previously demonstrated in the trial phase with a correct identification rate of 90% [ 12 ]. A signal equal to or lower than the background count does not necessarily mean that the sample is not radioactive, but could be a result of a higher background count that occurs occasionally or a low sample volume.…”

“…This illustrates the difficulty in the broad implementation of the technique. It is noteworthy that in most previous studies investigating the sensitivity of US-guided FNAC, FNAC was performed only if there was suspicion of metastasis on US examination [ 12 ]. This increases the likelihood of a positive FNAC considerably and explains some of the higher reported sensitivity rates, and might explain our sensitivity rate since we performed FNAC regardless of suspicion of metastasis on US examination.…”

“…Details of the study design and protocol have been published previously [ 12 ]. Briefly, the trial was designed as a prospective, multicentre, open-label, single-arm trial and was performed in two Dutch hospitals.…”

“…Power and sample size calculations are described in detail elsewhere [ 12 ]. Considering a 30% prevalence, the required sample size was 116 patients to detect metastatic SN(s) with a sensitivity of 90% and a 95% confidence interval (CI) of 80–100%, with a two-sided significance level α of 0.05 and a power 1 − β of 0.80.…”

“…Fine needle aspiration cytology (FNAC) with ultrasound (US) guidance may provide a good minimally invasive alternative. Several studies have focused on US examination with or without FNAC in melanoma patients, but sensitivity rates vary greatly and most studies lacked a method to accurately identify the SN prior to US examination and FNAC [ 12 ]. This problem could be overcome by using a hand-held gamma probe as an aid to US identification of the SN after lymphoscintigraphy.…”